A prototype dual laser system employing fluorescence spectroscopy for plaque recognition combined with a pulsed dye laser for tissue ablation was utilized to perform fluorescence guided, laser assisted balloon angioplasty in patients with femoro-popliteal occlusions. In 10 patients, we demonstrated successful real-time fluorescence-guided pulsed dye laser ablation of obstructions but noted difficulty with both laser and subsequent balloon angioplasty of heavily calcified lesions. This early clinical experience will permit us to modify delivery systems such that larger laser angioplasty channels may be created with increased catheter tip control. In addition, we have begun preliminary studies in patients with chronic total coronary occlusions using a similar fluorescence guided laser system. This will be the first attempt at percutaneous laser recanalization of chronic total coronary occlusions in humans and results are forthcoming.